Ronan Martin Griffin Berg

• MD DMSc
• Professor (Associate) at University of Copenhagen

Background: Severe immunopathology may drive the deleterious manifestations observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood. Objective: To phenotype leukocyte subpopulations and the cytokine milieu in the lungs and blood of critically ill patients with COVID-19 acute respiratory distress syndrome...

New findings: What is the topic of this review? The use of proning for improving pulmonary gas exchange in critically ill patients. What advances does it highlight? Proning places the lung in its 'natural' posture, and thus optimises the ventilation-perfusion distribution, which enables lung protective ventilation and the alleviation of potentiall...

Background: Many people recovering from COVID-19 experience prolonged symptoms, particularly breathlessness. We urgently need to identify safe and effective COVID-19 rehabilitative strategies. The aim of the current study was to investigate the potential rehabilitative role of inspiratory muscle training (IMT). Methods: 281 adults (46.6±12.2 yea...

A large proportion of patients suffer from a persistent reduction in cardiorespiratory fitness after recovery from COVID-19, of which the effects on the heart may potentially be reversed through the effect of high-intensity interval training (HIIT). In the present study, we hypothesized that HIIT would increase left ventricular mass (LVM) and impro...

In chronic obstructive pulmonary disease (COPD), the progressive loss of lung tissue is widely considered non-reversible. Thus, various treatment and rehabilitation schemes, including exercise-based pulmonary rehabilitation (PR) are thought to slow down but not reverse or halt the disease. Nonetheless, the adult lung conceals the intrinsic capacity...

Objective. To investigate the change in diffusing capacity from rest to submaximal exercise in patients with mild to severe COPD compared to a healthy, age- and sex matched control group, and to investigate if the diffusing capacity can be altered by high-intensity interval training (HIIT). Methods. 35 patients with COPD and 15 healthy age- and sex...

Regional citrate anticoagulation (RCA) is the preferred strategy for continuous renal replacement therapy (CRRT). However, impaired citrate metabolism, observed in patients with liver failure, mitochondrial dysfunction, and/or shock, can result in potentially lethal citrate accumulation (CA). We aimed to evaluate the ability of elevated lactate lev...

Purpose To investigate the efficacy of pulmonary blood volume (PBV) as a marker of the cardiac hyperemic response to adenosine during myocardial perfusion imaging (MPI). Methods Forty healthy subjects underwent four consecutive Rubidium‐82 rest/adenosine‐stress MPI: two sessions were conducted without any caffeine consumption (baseline), while the...

High-intensity interval training (HIIT) has shown to improve exercise capacity, symptom burden, and quality of life in COPD patients, but it remains to be investigated if HIIT can counteract limb muscle dysfunction. Therefore, we examined the impact of a 12-week supervised HIIT protocol on muscle oxygen conductance. Eight patients with mild to mode...

Background: Patients who have undergone double lung transplantation (DLTx) are at increased risk of pulmonary thromboembolism (PTE). Although the presence of clinically overt PTE can adversely affect short-term mortality, the prognostic impact of asymptomatic (silent) PTE detected by routine imaging after DLTx is unclear. Aim: This study aimed to...

The objective of the current review was to identify whether clinically established lung function metrics of ventilatory and diffusion capacity obtained by standardised methodology are consistent with superior lung function in athletes, and whether this is related to maximal oxygen uptake (V̇O2max). Three independent reviewers performed a literature...

Background Cardiopulmonary exercise testing (CPET) is usually considered the gold standard for assessing maximal oxygen consumption (V̇O 2max ), a health and performance marker in patients with chronic obstructive pulmonary disease (COPD). Despite the widespread application of CPET, the absolute and relative test‐retest reliability of CPET‐derived...

There is limited knowledge on diffusing capacity in scoliosis patients. It remains to be determined if impaired pulmonary diffusing capacity is mostly influenced by reduced alveolar–capillary membrane diffusing capacity (DM, CO), reduced pulmonary capillary blood volume (VC) or both. This study aims to report findings from dual test gas pulmonary d...

Background Ventilator‐associated pneumonia (VAP) may be a particular concern in patients with severe coronavirus disease 2019 (COVID‐19). We aimed to determine the prevalence and etiology of VAP in critically ill COVID‐19 patients in a Danish intensive care unit (ICU) during the first three waves of the COVID‐19 pandemic and to study associations b...

In patients previously hospitalised for COVID‐19, a 12‐week high‐intensity interval training (HIIT) intervention has previously been shown to increase left ventricular mass (LVM) immediately after the intervention. In the present study, we examined the effects of the same HIIT scheme on LVM, pulmonary diffusing capacity, symptom severity and functi...

After COVID‐19 long term respiratory symptoms and reduced lung function including maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) have been reported. However, no studies have looked at MIP and MEP in all disease groups and the reference materials collection methods differ substantially. We aimed to determine MIP and MEP in...

Doppler ultrasound may be used to assess leg blood flow (Q̇leg${{\dot{Q}}_{{\mathrm{leg}}}}$), but the reliability of this method remains unexplored in patients with chronic obstructive pulmonary disease (COPD), where between‐subject variability may be larger than healthy due to peripheral vascular changes. This study aimed to investigate the relia...

Whilst the exercise‐induced myokine interleukin‐6 (IL‐6) plays a beneficial role in cardiac structural adaptations, its influence on exercise‐induced functional cardiac outcomes remains unknown. We hypothesised that IL‐6 activity is required for exercise‐induced improvements in left ventricular global longitudinal strain (LV GLS). In an exploratory...

Reduced pulmonary diffusing capacity for carbon monoxide (DLCO) can be observed in pulmonary arterial hypertension (PAH) and associates with increased mortality. However, the prognostic value of DLCO when corrected for haemoglobin (DLCOc), an independent modifier of DLCO, remains understudied. Additionally, the prognostic role of ventilation (V)–pe...

In patients with chronic obstructive pulmonary disease (COPD), pulmonary vascular dysfunction and destruction are observable before the onset of detectable emphysema, but it is unknown whether this is associated with central hypovolemia. We investigated if COPD patients have reduced pulmonary blood volume (PBV) evaluated by ⁸² Rb-positron emission...

Transfer function analysis (TFA) is a widely used method for assessing dynamic cerebral autoregulation in humans. In the present study, we assessed the test–retest reliability of established TFA metrics derived from spontaneous blood pressure oscillations and based on 5 min recordings. The TFA‐based gain, phase and coherence in the low‐frequency ra...

Many patients exhibit persistently reduced pulmonary diffusing capacity after coronavirus disease 2019 (COVID‐19). In this study, dual test gas diffusing capacity for carbon monoxide and nitric oxide (DL,CO,NO) metrics and their relationship to disease severity and physical performance were examined in patients who previously had COVID‐19. An initi...

Background Type I interferon (IFN-I) and IFN autoantibodies play a crucial role in controlling SARS-CoV-2 infection. The levels of these mediators have only rarely been studied in the alveolar compartment in patients with COVID-19 acute respiratory distress syndrome (CARDS) but have not been compared across different ARDS etiologies, and the potent...

Endotoxin administration is commonly used to study the inflammatory response, and though traditionally given as a bolus injection, it can be administered as a continuous infusion over multiple hours. Several studies hypothesize that the latter better represents the prolonged and pronounced inflammation observed in conditions like sepsis. Yet very f...

The mean flow index—usually referred to as Mx—has been used for assessing dynamic cerebral autoregulation (dCA) for almost 30 years. However, concerns have arisen regarding methodological consistency, construct and criterion validity, and test–retest reliability. Methodological nuances, such as choice of input (cerebral perfusion pressure, invasive...

Type I interferon induced differences in exercise adaptations of aerobic capacity and fatigue in systemic lupus erythematosus-Protocol for a randomised controlled single-centre trial Protocol for a HIIT exercise trial illuminating exercise as intervention for aerobic capacity and fatigue, differentiating SLE patients on their type 1 IFN-signature...

We examined the extent to which apnoea‐induced extremes of oxygen demand/carbon dioxide production impact redox regulation of cerebral bioenergetic function. Ten ultra‐elite apnoeists (six men and four women) performed two maximal dry apnoeas preceded by normoxic normoventilation, resulting in severe end‐apnoea hypoxaemic hypercapnia, and hyperoxic...

Introduction It remains unclear whether long-term non-invasive ventilation (LT-NIV) for patients with chronic obstructive pulmonary disease (COPD) improves survival and reduces admissions as results from randomized trials are inconsistent. We aim to determine whether LT-NIV initiated after an admission with acute hypercapnic respiratory failure (AH...

Endotoxin administration is commonly used to study the inflammatory response, and though traditionally given as a bolus injection, it can be administered as a continuous infusion over multiple hours. Several studies hypothesize that the latter better represents the prolonged and pronounced inflammation observed in conditions like sepsis. Yet, very...

BACKGROUND: Voluntary asphyxia induced by apnea in competitive breath hold (BH) divers affords a unique opportunity to examine integrated mechanisms underlying the preservation of cerebral bioenergetic function. This study examined to what extent physiological extremes of oxygen (O2) demand and carbon dioxide (CO2) production impact redox homeostas...

Background: This study aimed to assess the feasibility of estimating the pulmonary blood volume noninvasively using standard Rubidium-82 myocardial perfusion imaging (MPI) and characterize the changes during adenosine-induced hyperemia. Methods: This study comprised 33 healthy volunteers (15 female, median age = 23 years), of which 25 underwent...

Alcoholic liver cirrhosis (ALC) is accompanied by sarcopenia. The aim of this study was to investigate the acute effects of balanced parenteral nutrition (PN) on skeletal muscle protein turnover in ALC. Eight male patients with ALC and seven age- and sex-matched healthy controls were studied for three hours of fasting followed by three hours of int...

Background: Patients with aneurysmal subarachnoid haemorrhage (SAH) might have impaired cerebral autoregulation, that is, CBF - and thereby oxygen delivery - passively increase with an increase in CPP. This physiological study aimed to investigate the cerebral haemodynamic effects of controlled blood pressure increase in the early phase after SAH...

Introduction The chronic inflammatory state in rheumatoid arthritis (RA) augments the risk of cardiovascular disease (CVD), with pro-inflammatory cytokines tumour necrosis factor (TNF) and interleukin 6 (IL-6) playing a vital role. Consequently, biological disease-modifying antirheumatic drugs (bDMARDs) may attenuate that risk. IL-6 is also a myoki...

Purpose: To investigate whether heterogeneous treatment effects occur for changes in inspiratory muscle strength, perceived dyspnoea, and health-related quality of life (QoL), following eight-weeks unsupervised home-based inspiratory muscle training (IMT) in adults with post-acute COVID-19 syndrome. Methods: In total, 147 adults with self-report...

Patients with severe traumatic brain injury (TBI) may have autonomic dysfunction, one manifestation of which is orthostatic intolerance. This potentially impairs physical rehabilitation. However, the exact mechanisms remain elusive. In 30 patients participating in a trial of early tilt training versus standard care and 15 healthy volunteers, 5-min...

Background To what extent sex‐related differences in cardiorespiratory fitness (CRF) impact postoperative patient mortality and corresponding implications for surgical risk stratification remains to be established. Methods To examine this, we recruited 640 patients (366 males vs. 274 females) who underwent cardiopulmonary exercise testing prior to...

Objectives High-intensity interval training (HIIT) during pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) may alleviate the symptom burden, but the fidelity and tolerability of HIIT using long or short intervals in patients with COPD are unknown. Methods Twelve patients with moderate-to-severe COPD were inclu...

Objective: To identify PaCO2 trajectories and assess their associations with mortality in critically ill patients with coronavirus disease 2019 (COVID-19) during the first and second waves of the pandemic in Denmark. Design: A population-based cohort study with retrospective data collection. Patients: All COVID-19 patients treated in eight int...

DLCO/NO, the combined single‐breath measurement of the diffusing capacity to carbon monoxide (DLCO) and nitric oxide (DLNO) measured either during exercise or in the resting supine position may be a useful physiological measure of alveolar–capillary reserve. In the present study, we investigated the between‐day test–retest reliability of DLCO/NO‐ba...

Post COVID-19 condition can occur following infection with SARS-CoV-2 and is characterised by persistent symptoms, including fatigue, breathlessness and cognitive dysfunction, impacting everyday functioning. This study explored how people living with post COVID-19 experienced an eight-week inspiratory muscle training (IMT) rehabilitation programme....

A large proportion of patients exhibit persistently reduced pulmonary diffusion capacity after COVID-19. It is unknown whether this is due to a post-COVID restrictive lung disease and/or pulmonary vascular disease. The aim of the current study was to investigate the association between initial COVID-19 severity and haemoglobin-corrected diffusion c...

Aim: Skeletal muscle convective and diffusive oxygen (O2) transport are peripheral determinants of exercise capacity in both patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). We hypothesised that differences in these peripheral determinants of performance between COPD and CHF patients are revealed during sm...

Dynamic cerebral autoregulation is often assessed by continuously recorded arterial blood pressure (ABP) and transcranial Doppler-derived mean cerebral blood flow velocity followed by analysis in the time and frequency domain, respectively. Sequential correlation (in the time domain, yielding e.g., the measure mean flow index, Mxa) and transfer fun...

Objective Invasively measured arterial blood pressure (ABP) is associated with complications, while non-invasively measured ABP is generally considered risk-free. This study aimed to investigate the reliability of non-invasive ABP measured using finger-cuff volume-clamp device compared to invasive ABP measured by an arterial catheter in patients wi...

Mechanisms of COVID-19-induced lung injury involve complex immunopathological events which are currently being elucidated. Studying immune mechanisms at the primary site of injury, i.e. the lower airways, are particularly informative. This review provides a brief introduction to the methods used to perform sampling from the lungs of critically ill...

The effects of dexamethasone (DXM) treatment on pulmonary immunity in COVID-19–associated acute respiratory distress syndrome (CARDS) remain insufficiently understood. We performed transcriptomic RNA-seq analysis of bronchoalveolar lavage fluid from 20 mechanically ventilated patients: 12 with CARDS (with or without DXM) and 8 non–COVID-19 critical...

New findings: What is the topic of this review? To explore the relationships and physiological mechanisms underlying the clinical benefits of cardiorespiratory fitness (CRF) in patients undergoing major intra-abdominal surgery. What advances does it highlight? Elevated CRF reduces postoperative morbidity/mortality, thus highlighting the importance...

Dynamic cerebral autoregulation to spontaneous fluctuations in cerebral perfusion pressure (CPP) is often assessed by transcranial Doppler (TCD) in the time domain, yielding primarily the mean flow index (Mx), or in the frequency domain using transfer function analysis (TFA), yielding gain and phase. For both domains, the measurement of blood press...

To provide novel data on surfactant levels in adult COVID-19 patients, we collected bronchoalveolar lavage fluid less than 72 h after intubation and used Fourier Transform Infrared Spectroscopy to measure levels of dipalmitoylphosphatidylcholine (DPPC). A total of eleven COVID-19 patients with moderate-to-severe ARDS (CARDS) and 15 healthy controls...

Introduction In the early phase after severe brain injury, patients are often bedridden in an attempt to control intracranial homeostasis; however, prolonged immobilisation may trigger complications. There is limited knowledge about the physiological effects of mobilisation in this early phase. Objective To investigate changes in brain tissue oxyg...

Background: It is unknown whether the complex immunopathogenesis of COVID-19 acute respiratory distress syndrome (CARDS) differs from that of non-COVID-19 ARDS. Moreover, the effects of systemic dexamethasone (DXM) treatment on pulmonary immunity in COVID-19 remain insufficiently understood. Objective: To understand immune regulation in the lungs o...

Introduction COVID-19 is associated with a marked systemic inflammatory response with concomitant cardiac injury and remodelling, but it is currently unknown whether the latter is reversible. Given that high-intensity interval training (HIIT) is a powerful stimulus to improve cardiorespiratory fitness while also eliciting marked anti-inflammatory e...

Understanding of strategies to support individuals recovering from coronavirus disease 2019 (COVID-19) is limited. ‘Long COVID’ is a multisystem disease characterised by a range of respiratory, gastrointestinal, cardiovascular, neurological, and musculoskeletal symptoms extending beyond 12 weeks. The aim of this study was to explore individuals’ ex...

Cerebral autoregulation is a complex mechanism that serves to keep cerebral blood flow relatively constant within a wide range of cerebral perfusion pressures. The mean flow index (Mx) is one of several methods to assess dynamic cerebral autoregulation, but its reliability and validity have never been assessed systematically. The purpose of the pre...

In patients with severe traumatic brain injury, there is limited evidence of the clinical effect of early orthostatic exercise, although such exercise may strengthen systemic or cerebral hemodynamic responses to head-up tilt, thereby minimizing orthostatic intolerance. We measured dynamic cerebral autoregulation (dCA) and the occurrence of orthosta...

Collaborative teaching strategies such as peer instruction and conventional group work have previously been shown to enhance meaningful learning, but they have not previously been compared. In this present study, we compared the impact of solving quizzes with peer instruction and conventional group work on immediate learning in a laboratory exercis...

Objectives: Many patients with COVID-19 suffer from persistent symptoms, many of which may potentially be reversed by high-intensity interval training (HIIT). Yet, the safety and tolerability of HIIT after COVID-19 is controversial. This study aimed to investigate the fidelity, tolerability and safety of three different HIIT protocols in individua...